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Unassigned

New Medicines

UptraviChronic thromboembolic pulmonary hypertension (CTEPH) - oral formulation

Information

Uptravi
Licence extension / variation
Janssen-Cilag
Actelion

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Non-prostanoid PGI2 receptor agonist
The prevalence of PAH is estimated at 15-52 per million. The incidences are estimated to be 1-3.3 per million per year for idiopathic PAH and 1.75-3.7 per million per year for chronic thromboembolic PH [1].
Chronic thromboembolic pulmonary hypertension (CTEPH) - oral formulation
Oral

UptraviPulmonary arterial hypertension (PAH) - IV formulation

Information

Uptravi
New formulation
Janssen-Cilag
Actelion

Development and Regulatory status

None
Phase III Clinical Trials
Approved (Licensed)
Yes
Sep 21The approved indication in the US is treatment of PAH (WHO Group I) to delay disease progression and reduce the risk of hospitalisation for PAH. Uptravi for injection is for use in patients who are temporarily unable to take oral therapy. It is given twice daily by intravenous infusion over 80 minutes at a dose that corresponds to the patient ’s current dose of Uptravi tablets [12].
Sep 21Janssen-Cilag does not appear to have any immediate plans to seek a licence for this formulation in the UK [10,11].
Jul 21Approved in US [8].
Sep 20Janssen submits NDA to FDA for selexipag as an injection for IV use for pulmonary arterial hypertension in adults with WHO functional class (FC) II–III, who are currently prescribed oral UPTRAVI but are temporarily unable to take oral therapy [7].
Jul 20EU filing no longer planned for 2020; no details provided of intentions [6].
Mar 20 In its latest pipeline update, Johnson & Johnson states it plans to file in EU & US in 2020 [5].
Apr 19No longer listed in planned submissions list for 2019; data expected from GRIPHON & AC-065A309 in 2019 [4]
Mar 19Company plans to file in US & EU in 2019 [2].
Mar 19Has orphan drug status in US [3].

Category

Non-prostanoid PGI2 receptor agonist
Prevalence of PAH is estimated at 15-52 per million. The incidences are estimated to be 1-3.3 per million per year for idiopathic PAH [1].
Pulmonary arterial hypertension (PAH) - IV formulation
Intravenous

Trial or other data

Sep 20The UPTRAVI IV study (NCT03187678) was a prospective, multi-center, open-label single-sequence cross–over, PIII study that examined a stable dose of UPTRAVI tablets to a corresponding dose of UPTRAVI for injection and switching back to UPTRAVI tablets. The treatment and observation phase was divided into 3 periods. In Period 1, patients received their stable oral dose of UPTRAVI twice daily (morning and evening of Day 1). In Period 2, patients received three infusions of corresponding UPTRAVI IV doses (morning and evening of Day 2, and morning of Day 3). In Period 3, patients resumed their stable oral UPTRAVI dose twice daily in the evening of Day 3 for 9 days, which was continued through the safety follow-up. Patients were hospitalized during Periods 1 and 2. All 20 enrolled patients completed the study as planned and received all UPTRAVI doses (oral or IV). The switch between oral UPTRAVI and UPTRAVI IV was well tolerated, and there were no unexpected safety findings. Adverse reactions that resulted from UPTRAVI for injection were similar to those associated with UPTRAVI tablets, with the exception of infusion site reaction. Prostacyclin-associated adverse events included headache, diarrhea, nausea, vomiting, pain in jaw, myalgia, pain in extremity, flushing and arthralgia [9].
May 18PIII trial that evaluated the safety, pharmacokinetics and tolerability of intravenous selexipag, following a switch from an oral dose of the drug, in patients with PAH completes (NCT03187678). The open-label trial enrolled 20 patients in the US and Germany [3].

Evidence based evaluations